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Table of Contents    
CASE REPORT
Year : 2021  |  Volume : 69  |  Issue : 3  |  Page : 740-743

Primary Central Nervous System Lymphoma Mimicking Wernicke's Encephalopathy


1 Department of Neurology, the 1st Medical Center of Chinese PLA General Hospital, Beijing, China
2 Department of Neurology, Aerospace Center Hospital, Beijing, China

Date of Submission12-Feb-2020
Date of Decision18-Aug-2020
Date of Acceptance12-Feb-2021
Date of Web Publication24-Jun-2021

Correspondence Address:
Dr. Dehui Huang
Department of Neurology, the 1st Medical Center of Chinese PLA General Hospital, Beijing
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0028-3886.319202

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 » Abstract 


Primary central nervous system lymphoma (PCNSL) is a rare disease that can be confused with Wernicke encephalopathy (WE). We have reported here the case of a 31-year-old malnourished man who presented with headache, fever, vomiting, diarrhea, and confusion. His imaging and laboratory findings were indicative of WE. His condition improved after treatment with a high dose of vitamin B1 and intravenous administration of methylprednisolone. However, after continuing to take vitamin B1 for 2 weeks, his symptoms and neuroimaging findings worsened. Increased standardized uptake values of positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG-PET) and interleukin-10 (IL-10) in the cerebrospinal fluid led to the diagnosis of PCNSL. After treatment with methotrexate and calcium leucovorin, the symptoms and neuroimaging abnormalities disappeared at the 6-month follow-up examination. The possibility of PCNSL should be considered if the routine treatment for WE are ineffective. 18F-FDG PET and IL-10 may provide a new method for the early diagnosis of PCNSL.


Keywords: IL-10, PCNSL, PET, Wernicke's encephalopathy
Key Messages: Primary central nervous system lymphoma (PCNSL) is a rare disease and may be confused with Wernicke encephalopathy (WE). Here, we have reported a rare case that was initially diagnosed as WE, but finally considered as PCNSL based on the 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography (18F-FDG-PET) findings and interleukin-10 (IL-10) level in the cerebrospinal fluid. Hence, the possibility of PCNSL should be considered if the regular treatment for WE is ineffective.


How to cite this article:
Wu L, Jin D, Huang D, Yu S. Primary Central Nervous System Lymphoma Mimicking Wernicke's Encephalopathy. Neurol India 2021;69:740-3

How to cite this URL:
Wu L, Jin D, Huang D, Yu S. Primary Central Nervous System Lymphoma Mimicking Wernicke's Encephalopathy. Neurol India [serial online] 2021 [cited 2021 Jul 28];69:740-3. Available from: https://www.neurologyindia.com/text.asp?2021/69/3/740/319202




Wernicke encephalopathy (WE) is a neurological disorder that presents with the classic triad of ophthalmoplegia, cerebellar dysfunction, and confusion. In certain instances, this condition may be confused with primary central nervous system lymphoma (PCNSL).[1],[2] Owing to its rarity and high malignancy, it is important to achieve an early diagnosis. Past reviews have revealed that other examinations such as 18F-fuorodeoxyglucose positron emission tomography (18F-FDG-PET) and the level of interleukin-10 (IL-10) in the cerebrospinal fluid (CSF)[3],[4],[5],[6] may facilitate an early diagnosis of PCNSL. Here, we have reported the case of a patient who was suspected to have WE, but was finally diagnosed with PCNSL based on neuroimaging studies, IL-10 levels, and therapeutic effects.


 » Case History Top


A 31-year-old man experienced intermittent headaches for over a month. The pain gradually worsened and was accompanied by watery stool, nausea, occasional vomiting, and a body temperature of up to 37.6°C. The patient did not have any significant medical, family, or psycho-social history. He had experienced anorexia 6 weeks before the start of symptoms and was malnourished at the time of treatment. He received anti-inflammatory therapy and fluid supplementation, but his symptoms aggravated to blurred vision and impairment of short-term memory. Neurological examination revealed slightly awkward speech, unstable walking, and reduced tendon reflexes. The CSF pressure was 145 mmH2O, with decreased chloride (107.1 mmol/L) and increased protein (712.2 mg/L) levels. Cranial magnetic resonance (MR) imaging showed hyperintense signals next to the grey matter around the third ventricle on T2WI and fluid attenuated inversion recovery (FLAIR) sequences, especially in the anterior and medial dorsal nucleus of the left thalamus [Figure 1]a, [Figure 1]b, [Figure 1]c. The hypothalamus region next to the third ventricle was partially enhanced [Figure 1]d. The patient was suspected to have WE and was accordingly treatment with high-dose vitamin B and 240-mg intravenous dose of methylprednisolone once. A week later, his symptoms and a repeat MRI finding indicated improvement [Figure 1]e.
Figure 1: Cranial MR scan at the patient's first visit. Hyperintense signals can be seen in the bilateral thalami on T2WI (a and b) and FLAIR (c) sequences. On contrast-enhanced imaging, the lesion in the thalamus indicated no enhancement, while the areas around the third ventricle showed slight enhancement on coronal sections (d). The lesions improved after treatment with vitamin B and intravenous methylprednisolone (e)

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After 10 days, the patient returned with recurrent headache. He experienced somnolence and impaired memory and orientation, and his body temperature fluctuated from 37°C to 38°C. He fell into a state of continuous confusion, with a Tmax of up to 40°C within a few days. Neurological examination revealed drowsiness, MRC Grade 4 + muscle strength, absence of tendon reflexes, and positive bilateral Babinski signs. His blood tests indicated neutrophils 47.4%, lymphocytes 42.3%, erythrocyte sedimentation rate 29 mm/h, and procalcitonin 0.069 ng/mL. The tumor marker levels and bacterial smears were normal. Antibodies to autoimmune encephalitis were all negative. Other findings included CSF pressure 185 mmH2O, white blood cell count 17 × 106/L, chloride 125.0 mmol/L, glucose 2.6 mmol/L, protein 2004.4 mg/L, IL-6 178.0 pg/mL, and IL-10 479.0 pg/mL. Another brain MRI scan revealed symmetrical mass-effect signals in the bilateral hypothalamic and posterior limb of the internal capsule on T2WI [Figure 2]a and [Figure 2]b. The signals were decreased in terms of apparent diffusion coefficient [ADC, [Figure 2]c. An obvious clump-like enhancement could be observed in the sella turcica [Figure 2]e, [Figure 2]f, [Figure 2]g. Lipid peaks were detected on MR spectroscopy [Figure 2]i. 18F-FDG PET revealed the presence of a round lesion in the sella turcica with a high density and an SUVmax of 61.1, which strongly indicated the possibility of PCNSL [Figure 2]h. As his family refused a brain biopsy, we commenced a trial treatment with high-dose methotrexate (5 g/m2/24 h) with leucovorin calcium (0.05 g q6h) on the basis of methylprednisolone 80 mg/day. After treatment, his consciousness impairment and fever gradually improved. After 1 month of the chemotherapy, the lesions almost completely disappeared on a repeat contrast MRI examination [Figure 2]i. At the 6-month follow-up examination, the patient had returned to normalcy.
Figure 2: Another cranial MRI scan showing lesions in the bilateral hypothalamic and posterior limb of the internal capsule, which were substantially exacerbated 1 week after discharge (a and b). A lesion in the Sella turcica showed low ADC values (c). Cranial CT showed a round-shaped lesion with high density (d). Contrast-enhanced MRI showing a round-shaped tumor with strong and homogenous contrast enhancement (e-g). 18F-FDG-PET-CT showing that the lesion in the Sella turcica had a remarkably high glucose metabolism rate, with an SUVmax of 61.1 (h). MR spectroscopy showed a lipid peak (arrow) resonating at a chemical shift of 1.3 pp (j). After chemical and steroid therapy, the lesion had almost disappeared (i)

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 » Discussion Top


We have reported here a case of PCNSL that was finally considered through cranial CT, MRI, 18F-FDG-PET, and assessment of cytokine levels in the CSF. Although pathological findings were lacking, the effectiveness of chemotherapy supported the diagnosis. Initial misdiagnosis of the condition as WE is attributable to the deceptive history of the patient and the presenting radiological features. In addition, typical signs such as nystagmus and ophthalmoplegia were missing. The grey matter around the cerebral aqueduct was spared, and the symptoms worsened during standard vitamin supplementation. In addition, the imaging characteristics of this case progressed rapidly from asymmetrical lesions to mass-effect lesions with severe edema, strong and homogenous contrast enhancement, limited ADC diffusion, and no signs of necrosis. These specific imaging features indicated PCNSL.[7] This condition should be strongly considered even in the absence of imaging and histopathological evidence of the lesion in some circumstances when the response to corticosteroid therapy is striking.[8] The obfuscating initial improvement in our case may be related to the use of corticosteroids. The dramatic disappearance of a lesion may sometimes be used as an implicit evidence of the existence of PCNSL, although the final diagnosis mainly depends on the radiographic appearance and brain biopsy specimen. Unfortunately, biopsy is not only invasive but also difficult to achieve in the early stage of the disease. Hence, the other options gain prominence in the diagnosis. B-cell lymphoma releases a substantial quantity of IL-10, which plays various roles in the development of the disease and could be viewed as one of the biomarkers of PCNSL. Whitcup et al. reported that an IL-10/IL-6 ratio >1 was associated with CNS lymphoma.[5] Sasayama et al. compared 31 cases of PCNSL and 59 cases of other CNS tumors, demonstrating a sensitivity of 71.0% and a specificity of 100% using an IL-10 cut-off level of 9.5 pg/mL in the CSF to differentiate PCNSL from other tumors.[6] The IL-10 level in the CSF of our patient was quite high (>400 pg/mL), which is consistent with the observations reported by past studies.[5],[6] When compared with the normal tissues and other intracranial tumors, PCNSL has a higher cellular density and an increased glucose metabolism rate. This intense uptake of glucose, with an SUV that is usually 2.5-times greater than the average value of normal tissues, makes 18F-FDG-PET a promising indicator of PCNSL.[3] PET-CT has become an integral part of assessing patients with oncological disorders.[9] Makino et al. stated that the SUVmax cut-off value should be set at 12,[4] while Liu et al. found that the SUVmax value in immunocompetent patients with PCNSL ranges from 11.7 to 44.1 and proposed that either an SUVmax >15 or a tumor-to-normal contralateral cortex activity ratio of >4 is a strong indicator of PCNSL.[8] In our case, the lesion had a remarkably elevated SUVmax value of 61.1, which strongly supports the probable diagnosis of PCNSL. Pathology is the golden standard for diagnosing neoplastic diseases. However, owing to the rapid progression of the disease in our patient and the unwillingness of the family members, we were unable to perform a biopsy or CSF cytology. Nonetheless, based on the available examination results, that is, cranial CT high-density lesions, midline lesions, mass-like substantial enhancement, elevated SUV value, and IL-10 in the CSF, we diagnosed PCNSL. In addition, the effect of steroid therapy was dramatic, which immensely supported our diagnosis.

In summary, our case suggests that if the treatment effect is poor or if the symptoms relapse in patients tentatively diagnosed with WE and receiving regular thiamine supplementation, the possibility of PCNSL should be considered. The IL-10 levels in the CSF and 18F-FDG-PET scan are helpful in the early diagnosis of PCNSL.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 » References Top

1.
Boniol S, Boyd M, Koreth R, Burton GV. Wernicke encephalopathy complicating lymphoma therapy: Case report and literature review. South Med J 2007;100:717-9.  Back to cited text no. 1
    
2.
Shiels MS, Pfeiffer RM, Besson C, Clarke CA, Morton LM, Nogueira L, et al. Trends in primary central nervous system lymphoma incidence and survival in the U.S. Br J Haematol 2016;174:417-24.  Back to cited text no. 2
    
3.
Kawai N, Miyake K, Yamamoto Y, Nishiyama Y, Tamiya T. 18F-FDG PET in the diagnosis and treatment of primary central nervous system lymphoma. Biomed Res Int 2013;2013:247152.  Back to cited text no. 3
    
4.
Makino K, Hirai T, Nakamura H, Murakami R, Kitajima M, Shigematsu Y, et al. Does adding FDG-PET to MRI improve the differentiation between primary cerebral lymphoma and glioblastoma? Observer performance study. Ann Nucl Med 2011;25:432-8.  Back to cited text no. 4
    
5.
Whitcup SM, Stark-Vancs V, Wittes RE, Solomon D, Podgor MJ, Nussenblatt RB, et al. Association of interleukin 10 in the vitreous and cerebrospinal fluid and primary central nervous system lymphoma. Arch Ophthalmol 1997;115:1157-60.  Back to cited text no. 5
    
6.
Sasayama T, Nakamizo S, Nishihara M, Kawamura A, Tanaka H, Mizukawa K, et al. Cerebrospinal fluid interleukin-10 is a potentially useful biomarker in immunocompetent primary central nervous system lymphoma (PCNSL). Neuro Oncol 2012;14:368-80.  Back to cited text no. 6
    
7.
Schlegel U. Primary CNS lymphoma. Ther Adv Neurol Disord 2009;2:93-104.  Back to cited text no. 7
    
8.
Liu D, Kong Z, Wang Y, Chen W, Liu L, Dang Y, et al. Quantitative and visual characteristics of primary central nervous system lymphoma on 18F-FDG-PET. Interdiscip Sci 2019;11:300-6.  Back to cited text no. 8
    
9.
Lövblad K-O, Bouchez L, Altrichter S, Ratib O, Zaidi H, Vargas MI. PET-CT in neuroradiology. Clin Transl Neurosci, 2019. https://doi.org/10.1177/2514183X19868147.  Back to cited text no. 9
    


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